4-Methylmorpholine → HCID 86669940, compound

HRID 1506547Notes

Reaction equation

HRID 1506547 reaction equation
[OH:1][CH:2]([C:6]1[CH:7]=[C:8]2[C:25](=[CH:26][CH:27]=1)[C:12]1=[N:13][O:14][C:15]([C:16]3[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][CH3:24])=[CH:18][CH:17]=3)=[C:11]1[CH2:10][CH2:9]2)[C:3](O)=[O:4].CN1CCOCC1.[NH2:35][CH2:36][C:37]#[N:38].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C>[C:36]([CH2:37][NH:38][C:3](=[O:4])[CH:2]([OH:1])[C:6]1[CH:7]=[C:8]2[C:25](=[CH:26][CH:27]=1)[C:12]1=[N:13][O:14][C:15]([C:16]3[CH:17]=[CH:18][C:19]([CH2:22][CH2:23][CH3:24])=[CH:20][CH:21]=3)=[C:11]1[CH2:10][CH2:9]2)#[N:35]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 10901AminoacetonitrileHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 67170951HCID 67170951, compound

Product 1

HCID 86669940HCID 86669940, compoundYield 47.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-hydroxy-2-(3-(4-propylphenyl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)acetic acid (Example 127, 20 mg, 0.055 mmol) in DMF (1 mL) was added 4-methylmorpholine (0.036 mL, 0.33 mmol), 2-aminoacetonitrile (5.55 mg, 0.1 mmol) and BOP (43.8 mg, 0.1 mmol). The reaction mixture was stirred overnight and was then purified by preparative HPLC (Phenomenex Luna 5 u C18 21.2×100 mm, Solvent A: 90% water with 10% MeOH and 0.1% TFA, Solvent B: 90% MeOH with 10% water and 0.1% TFA, Gradient: 0% B to 100% B over 10 min, 20 mL/min, 220 nM, product retention time=11.9 min) to give N-(cyanomethyl)-2-hydroxy-2-(3-(4-propylphenyl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)acetamide (11.2 mg, 0.026 mmol, 46.9% yield): product HPLC ret. time=9.89 min. (condition G); LC/MS M+1=402.1; 1H NMR (400 MHz, CD3OD) δ ppm 7.88 (1H, d, J=7.92 Hz), 7.72 (2H, d, J=8.36 Hz), 7.43-7.53 (2H, m), 7.37 (2H, d, J=8.36 Hz), 5.13 (1H, s), 4.19 (2H, d, J=1.76 Hz), 3.06 (4H, s), 2.67 (2H, t, J=7.59 Hz), 1.62-1.77 (2H, m), 0.97 (3H, t, J=7.37 Hz).

Workup

  1. customwas then purified by preparative HPLC (Phenomenex Luna 5 u C18 21.2×100 mm, Solvent A: 90% water with 10% MeOH and 0.1% TFA, Solvent B: 90% MeOH with 10% water and 0.1% TFA, Gradient: 0% B to 100% B over 10 min, 20 mL/min, 220 nM, product retention time=11.9 min)

Sources & evidence

ORD record
ord-95126a736c3d4ad8ae1f88e3276c3bc6
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

Loading…